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Epigenetics of prostate cancer: beyond DNA methylation

Epigenetic mechanisms permit the stable inheritance of cellular properties without changes in DNA sequence or amount. In prostate carcinoma, epigenetic mechanisms are essential for development and progression, complementing, amplifying and diversifying genetic alterations. DNA hypermethylation affec...

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Detalles Bibliográficos
Autores principales: Schulz, W A, Hatina, J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Ltd 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3933104/
https://www.ncbi.nlm.nih.gov/pubmed/16563224
http://dx.doi.org/10.1111/j.1582-4934.2006.tb00293.x
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author Schulz, W A
Hatina, J
author_facet Schulz, W A
Hatina, J
author_sort Schulz, W A
collection PubMed
description Epigenetic mechanisms permit the stable inheritance of cellular properties without changes in DNA sequence or amount. In prostate carcinoma, epigenetic mechanisms are essential for development and progression, complementing, amplifying and diversifying genetic alterations. DNA hypermethylation affects at least 30 individual genes, while repetitive sequences including retrotransposons and selected genes become hypomethylated. Hypermethylation of several genes occurs in a coordinate manner early in carcinogenesis and can be exploited for cancer detection, whereas hypomethylation and further hypermethylation events are associated with progression. DNA methylation alterations interact with changes in chromatin proteins. Prominent alterations at this level include altered patterns of histone modification, increased expression of the EZH2 polycomb histone methyltransferase, and changes in transcriptional corepressors and coactivators. These changes may make prostate carcinoma particularly susceptible to drugs targeting chromatin and DNA modifications. They relate to crucial alterations in a network of transcription factors comprising ETS family proteins, the androgen receptor, NKX3.1, KLF, and HOXB13 homeobox proteins. This network controls differentiation and proliferation of prostate epithelial cells integrating signals from hormones, growth factors and cell adhesion proteins that are likewise distorted in prostate cancer. As a consequence, prostate carcinoma cells appear to be locked into an aberrant state, characterized by continued proliferation of largely differentiated cells. Accordingly, stem cell characteristics of prostate cancer cells appear to be secondarily acquired. The aberrant differentiation state of prostate carcinoma cells also results in distorted mutual interactions between epithelial and stromal cells in the tumor that promote tumor growth, invasion, and metastasis.
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spelling pubmed-39331042015-07-06 Epigenetics of prostate cancer: beyond DNA methylation Schulz, W A Hatina, J J Cell Mol Med Invited Review-Epigenetic Review Series Epigenetic mechanisms permit the stable inheritance of cellular properties without changes in DNA sequence or amount. In prostate carcinoma, epigenetic mechanisms are essential for development and progression, complementing, amplifying and diversifying genetic alterations. DNA hypermethylation affects at least 30 individual genes, while repetitive sequences including retrotransposons and selected genes become hypomethylated. Hypermethylation of several genes occurs in a coordinate manner early in carcinogenesis and can be exploited for cancer detection, whereas hypomethylation and further hypermethylation events are associated with progression. DNA methylation alterations interact with changes in chromatin proteins. Prominent alterations at this level include altered patterns of histone modification, increased expression of the EZH2 polycomb histone methyltransferase, and changes in transcriptional corepressors and coactivators. These changes may make prostate carcinoma particularly susceptible to drugs targeting chromatin and DNA modifications. They relate to crucial alterations in a network of transcription factors comprising ETS family proteins, the androgen receptor, NKX3.1, KLF, and HOXB13 homeobox proteins. This network controls differentiation and proliferation of prostate epithelial cells integrating signals from hormones, growth factors and cell adhesion proteins that are likewise distorted in prostate cancer. As a consequence, prostate carcinoma cells appear to be locked into an aberrant state, characterized by continued proliferation of largely differentiated cells. Accordingly, stem cell characteristics of prostate cancer cells appear to be secondarily acquired. The aberrant differentiation state of prostate carcinoma cells also results in distorted mutual interactions between epithelial and stromal cells in the tumor that promote tumor growth, invasion, and metastasis. John Wiley & Sons, Ltd 2006-01 2007-03-15 /pmc/articles/PMC3933104/ /pubmed/16563224 http://dx.doi.org/10.1111/j.1582-4934.2006.tb00293.x Text en
spellingShingle Invited Review-Epigenetic Review Series
Schulz, W A
Hatina, J
Epigenetics of prostate cancer: beyond DNA methylation
title Epigenetics of prostate cancer: beyond DNA methylation
title_full Epigenetics of prostate cancer: beyond DNA methylation
title_fullStr Epigenetics of prostate cancer: beyond DNA methylation
title_full_unstemmed Epigenetics of prostate cancer: beyond DNA methylation
title_short Epigenetics of prostate cancer: beyond DNA methylation
title_sort epigenetics of prostate cancer: beyond dna methylation
topic Invited Review-Epigenetic Review Series
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3933104/
https://www.ncbi.nlm.nih.gov/pubmed/16563224
http://dx.doi.org/10.1111/j.1582-4934.2006.tb00293.x
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